CHEM2232 EXAM 2

Aromaticity criteria

cyclic, planar, fully conjugated, (4n+2) π electrons

Hückel’s rule

aromatic if (4n+2) π electrons, antiaromatic if 4n

Antiaromatic vs. nonaromatic

anti = planar + conjugated + 4n π
non = not fully conjugated or not planar

Frost circle purpose

determines aromaticity via MO energy levels; line up one corner in the middle of the circle

Frost circle rule

if all bonding MOs filled → aromatic

General EAS mechanism

electrophile attack → arenium ion → deprotonation restores aromaticity

Rate-determining step in EAS

formation of arenium ion

Activating groups

(EDG) donate electrons, increase rate, ortho/para directing

Deactivating groups

(EWG) withdraw electrons, decrease rate, meta directing

Halogens directing effect

ortho/para directors but deactivating

Ortho/para directors

-OH, -NH₂, -OR, alkyl

Meta directors

-NO₂, -CF₃, -SO₃H, carbonyls (-COR)

Blocking group purpose

control substitution position

Common blocking group

H₂SO₄, SO₃ → SO₃H (sulfonation)

How to remove SO₃H

heat with H⁺, H₂O (desulfonation)

Why protect -NH₂ or -OH

too activating → causes polysubstitution

Common protection for amines

acylation (amide formation)

Kinetic product

forms faster, lower temp, less stable

Thermodynamic product

more stable, higher temp

1,2-addition

kinetic product

1,4-addition

thermodynamic product

Diels-Alder reaction

[4+2] cycloaddition between diene and dienophile

Endo rule

electron-withdrawing groups go endo (preferred)

Diene requirement

must be s-cis

Dienophile requirement

electron-poor alkene

Electrocyclic reaction

ring opening/closing via π electrons

4n system (thermal)

conrotatory

4n+2 system (thermal)

disrotatory

Halogenation of benzene

Br₂/FeBr₃ or Cl₂/FeCl₃ → substitution

Nitration

HNO_₃, H₂SO₄ → NO₂ added

Sulfonation

SO₃, H₂SO₄ → SO₃H added

Hydrogenation

benzene + H₂, Pd-C → cyclohexane

Friedel-Crafts alkylation

R-Cl, AlCl₃ → adds alkyl group

Limitations of Friedel-Crafts alkylation

rearrangements occur

Friedel-Crafts alkylation fails when

strong deactivators present

Friedel-Crafts acylation

acyl chloride/AlCl3 → adds ketone

Advantage of Friedel-Crafts acylation

no rearrangement

Nitro → amine

reduction (H₂, Pd-C or Fe or Zn, HCl)

Clemmensen reduction

carbonyl + Zn(Hg), HCl → alkane

Wolff-Kishner reduction

carbonyl + NH₂NH₂, EtOH, heat → alkane (basic conditions)
use when acetal is present (protected ketone/aldehyde)

Benzylic oxidation

• Ar–CH₃ → Ar–COOH

• Ar–CH₂R → Ar–COOH

• Ar–CHR₂ → Ar–COOH

CrO₃, H₂SO₄, H₂O

PCC

alcohol (-OH) → aldehyde/ketone (no overoxidation)

Chromic acid (CrO₃, H₂SO₄, H₂O)

alcohol (-OH) → carboxylic acid (-COOH)

Ozonolysis

1) O₃, CH₂Cl₂
2) S(CH₃)₂

splits double bond → carbonyls (ketone/aldehyde)

Alkyne hydration (Markovnikov)

alkyne + HgSO₄, H₂SO₄, H₂O → ketone

Alkyne hydration (anti-Markovnikov)

internal alkyne + 1) BH₃, THF; 2) NaOH, H₂O₂, H₂O → ketone
terminal alkyne + 1) BH₃, THF; 2) NaOH, H₂O₂, H₂O → aldehyde

Hydride reduction (LiAlH₄, strongest/NaBH₄, mild)

LiAlH₄ reduces aldehydes, ketones, esters, and carboxylic acids → alcohols
amides/nitriles to amine

NaBH₄ reduces aldehydes, ketones → alcohols

Organometallic addition (RMgX,

Hydrate formation

carbonyl + water → geminal diol (2 -OH groups attached to the same carbon atom)

Hemiacetal

carbonyl + alcohol (1 eq) → 1 -OH, 1 -OR

Acetal

carbonyl + alcohol (2 eq, acid) → 2 -OR

Acetal purpose

protecting group for aldehydes and ketones (acidic conditions)

Acetal hydrolysis

H⁺+ water → carbonyl

Thioacetal formation & purpose

carbonyl + thiol (-RSH)
used as a protecting group for ketones and aldehydes (basic conditions—use when molecule is acid-sensitive)

Thioacetal removal

H₂, RaNi

Imine formation

carbonyl + primary amine (acidic conditions)

Enamine formation

carbonyl + secondary amine (acidic conditions)

Imine/enamine → carbonyl

H⁺, H₂O

Cyanohydrin formation

carbonyl + CN⁻ → adds -CN + -OH

Wittig reaction

aldehyde/ketone + R-PPh₃ → alkene

How to approach EAS problems

identify directing groups → predict position

How to approach synthesis

work backwards from product

Biggest Friedel-Crafts mistake

ignoring rearrangement

Most important carbonyl concept

protecting groups (acetals)

Most tested pattern

EAS + carbonyl combined synthesis